How can polypharmacy (use of multiple medications) contribute to foot pain and what management strategies can be implemented?

Foot Pain Related to Polypharmacy

Polypharmacy contributes to foot pain primarily through adverse drug reactions (ADRs) that cause lower extremity pain, drug-induced peripheral neuropathy, and medication-related falls that lead to foot injuries—requiring systematic medication review and deprescribing of high-risk agents.

How Polypharmacy Causes Foot Pain

Direct Medication-Related Mechanisms

Lower extremity pain is a recognized fall risk factor in the P-SCHEME acronym (Pain-axial or lower extremity), which clinicians should systematically assess when evaluating mobility impairment in patients on multiple medications 1. The connection operates through several pathways:

• Drug-induced peripheral neuropathy can develop from medications commonly used in polypharmacy regimens, particularly statins, which may cause myalgia extending to the lower extremities 1
• NSAIDs used to treat pain (including foot pain) can create a prescribing cascade where these medications worsen hypertension or heart failure, leading to edema and additional lower extremity discomfort 1
• Anticholinergic medications contribute to functional decline and mobility impairment, indirectly affecting foot health through reduced activity and gait abnormalities 1

Indirect Mechanisms Through Falls and Functional Decline

The rate of falls increases by 21% in patients taking 4 or more medications and by 50% in those taking 10 or more drugs, with falls frequently resulting in foot and lower extremity injuries 1. This creates a vicious cycle where:

• Falls lead to foot trauma and pain
• Pain medications are added to the regimen
• Additional medications further increase fall risk
• Functional capacity declines, worsening foot biomechanics 1

The Prescribing Cascade Problem

Any new symptom in older people should be considered a possible ADR until proven otherwise 1. Foot pain may trigger inappropriate prescribing when:

• OTC NSAIDs are added for foot pain, worsening cardiovascular or renal disease 1
• The foot pain itself may be an ADR misinterpreted as a new condition 1
• Additional medications prescribed for pain increase the total medication burden 1

Management Strategy Algorithm

Step 1: Comprehensive Medication Reconciliation

Create an accurate medication list at every visit including all prescriptions, over-the-counter medications, supplements, and herbal remedies 2, 3. Specifically document:

• All analgesics (prescribed and OTC)
• NSAIDs that may worsen cardiovascular/renal function
• Statins that may cause myalgia
• Medications affecting balance and fall risk 1

Step 2: Identify Drug-Related Causes of Foot Pain

Screen for high-risk medications using the Beers Criteria or STOPP/START tools 2, 3. Priority targets include:

• Statins: Assess for myalgia extending to lower extremities 1
• NSAIDs: Evaluate for drug-disease interactions with heart failure, chronic kidney disease, or hypertension that may cause edema and foot discomfort 1, 2
• Medications causing peripheral neuropathy: Review all agents with this potential
• Sedatives/hypnotics, benzodiazepines, opioids: These increase fall risk leading to foot trauma 1, 2

Step 3: Assess Drug-Drug and Drug-Disease Interactions

Use interaction databases to identify combinations that may contribute to foot pain or fall risk 2, 3:

• QT-prolonging drugs that cause syncope and falls
• Anticoagulants increasing bleeding risk from minor foot trauma
• Antihypertensives causing orthostatic hypotension and falls 1

Identify drug-disease interactions where medications worsen conditions affecting the feet 2:

• NSAIDs in patients with heart failure (causing edema)
• Sulfonylureas in chronic kidney disease (causing hypoglycemia and falls)
• Diuretics causing electrolyte imbalances and muscle cramps 1

Step 4: Implement Deprescribing

Target medications where potential harm outweighs benefit, starting with the highest-risk agents 1, 2:

• Discontinue or reduce NSAIDs if causing cardiovascular or renal complications that contribute to lower extremity symptoms 1
• Taper benzodiazepines and opioids that increase fall risk using gradual dose reduction 1, 2
• Consider statin alternatives or dose reduction if myalgia is present 1
• Eliminate medications from the prescribing cascade that were added to treat ADRs 1

The deprescribing process requires:

• Patient and family education about risks 2
• Agreement from all parties 2
• Gradual tapering rather than abrupt discontinuation 2

Step 5: Optimize Remaining Medications

Start pharmacological treatment at low doses and gradually titrate upward based on clinical response, as more than 80% of serious ADRs are dose-dependent and potentially avoidable 1. For foot pain specifically:

• Acetaminophen is preferred over NSAIDs in older adults with polypharmacy due to lower interaction risk (though hepatotoxicity remains a concern at high doses) 4
• Topical medications for localized foot pain minimize systemic drug burden 5
• Gabapentin or tricyclic antidepressants for neuropathic foot pain, but monitor for anticholinergic effects and sedation 5

Step 6: Address Fall Risk and Mobility

Refer to physical therapy for exercise programs that improve balance and strength (tai chi, walking, resistance training) to prevent falls and maintain foot function 1. Evaluate:

• Footwear characteristics (suboptimal shoes contribute to falls) 1
• Need for walking aids 1
• Environmental modifications 1

Step 7: Monitor and Follow-Up

Schedule regular follow-up to assess medication effectiveness and adverse effects, with increased frequency during care transitions 3. Specifically monitor:

• Resolution or persistence of foot pain
• New falls or mobility decline
• Adherence using validated tools like the Morisky Medication Adherence Scale 1, 2
• Renal function for dose adjustments 2

Critical Pitfalls to Avoid

Do not focus solely on the number of medications rather than appropriateness 2. A patient may need multiple medications, but each must have a clear indication.

Do not abruptly discontinue medications without proper tapering, particularly benzodiazepines and opioids 2.

Do not overlook non-prescription medications and supplements that contribute to drug interactions and ADRs 2.

Do not add new medications for foot pain without first considering whether existing medications are causing the symptom 1. This prevents the prescribing cascade.

Do not ignore patient preferences and treatment goals when making deprescribing decisions 2, 3.

Team-Based Approach

Utilize clinical pharmacists for comprehensive medication reviews when available, as they can identify and reduce potentially inappropriate medications by 36.4% 1, 2. Coordinate care among multiple prescribers to prevent duplication and ensure all providers are aware of the complete medication regimen 2, 3.